Mucociliary clearance of inhaled particles from the tracheobronchial tree is an important defense mechanism of the lung. A failure of this clearance mechanism results in retained mucous secretions and a predisposition to pulmonary infection. Circumstantial evidence indicates that a balance in the rate of secretions of ions, water and mucous glycoproteins by the airway epithelium help regulate mucociliary clearance. It is thought that a major portion of the total airway secretions are produced by the submucosal glands of the airway epithelium. Thus, alterations in the mechanisms controlling glandular secretions may be involved in the failure of mucociliary clearance in certain pulmonary diseases. Prior studies of the control of secretion by the airway epithelium have generally employed intact tracheal tissue, in vitro. The use of intact tissue has hindered the ability of investigators to adequately separate the physiological responses of gland cells from those of the surface epithelium. I have developed a technique to isolate viable submucosal gland cells from cat trachea. In the proposed studies, the presence of cholinergic and adrenergic receptors in glandular cell homogenates will be determined using radiolabelled ligands. Receptors to be characterized, if present, include muscarinic cholinergic, Alpha-adrenergic and Beta-adrenergic receptors. I will also study mucous glycoprotein secretion by isolated gland cells. Changes in mucous glycoprotein secretion rates in response to tracheal secretagogues will be determined. Secreted mucous glycoproteins will be characterized biochemically. I also plan to determine if the cyclic nucleotides (cyclic AMP and cyclic GMP) are involved in secretagogue-induced secretion by these cells. Once normal secretory function is defined, the effects of viral infection (influenza type A and respiratory syncytial virus) on the rate and control of mucous glycoprotein secretion will be studied.